On the mechanism of noradrenaline-induced prostaglandin E2-Synthesis in primary cell cultures from rabbit splenic pulpa.
The role of Ca2+ and phospholipase A2 in alpha-adrenoceptor mediated stimulation of prostaglandin (PG)E2-release was investigated in primary cell cultures of rabbit splenic pulpa. Noradrenaline enhanced PGE2-release only in the presence of extracellular Ca2+. In contrast, PGE2-release induced by arachidonic acid was unchanged when Ca2+ was omitted. In the presence of Ca2+, the ionophore A 23187 increased PGE2-release concentration-dependently. During incubation in Ca2+-free medium, the ionophore was ineffective. Inhibitors of phospholipase A2 (mepacrine, p-bromophenacyl bromide) abolished the noradrenaline-induced PGE2-release and reduced the effect of A 23187; the stimulation of PGE2-release by arachidonic acid was not affected. Addition of exogenous phospholipase A2 enhances release of PGE2. From these results we suggest that noradrenaline-induced PGE2-release in rabbit splenic fibroblasts via alpha-adrenoceptors involves the following steps: influx of Ca2+, activation of a Ca2+-dependent phospholipase and liberation of arachidonic acid which is transformed into PGs.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D015232:Dinoprostone; D005347:Fibroblasts / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011458:Prostaglandins E / Q000096:biosynthesis*; D011817:Rabbits; D013154:Spleen / Q000378:metabolism*
D001095:Arachidonic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D000001:Calcimycin; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D002118:Calcium; D009638:Norepinephrine